Loci mapping in the I region of the H-2 gene complex of the mouse play a major role in the regulation of immune responses. Ir and Is loci govern the capacity to generate or suppress responses to a variety of foreign antigens, and Ia loci control cell surface determinants which appear to serve as structures used by lymphocytes to interact with and regulate on another. Before the precise function mediated by the products of these loci can be evaluated, the cellular site of expression of each locus must be resolved. In this research proposal, a systematic analysis of the expression of separate Ia loci in functionally different lymphocyte subpopulations will be conducted. A knowledge of the lymphocyte subclass distribution of products controlled by these loci, coupled with an understanding of the functions mediated by these cells and the cellular interactions leading to the generation or suppression of immunity, will lay the ground work for testing the precise role each product plays in the immune response.